Both the heterogeneity and mechanisms of triggering of lymphocytes will be studied, using a variety of in vitro techniques. T-lymphocytes at various stages of maturation will be defined using the criteria of life-time and recirculation properties. The role of antigen in the progression of T-lymphocytes through these stages will be examined. The heterogeneity of T-lymphocytes responsible for helper activity will be studied using sensitivity to tolerance, cross-tolerance, and cross-reactivity to define at least two subpopulations. The mechanism of B-lymphocyte triggering by lipopolysaccharide (LPS) or antigen and T-cell factors will be studied. The role of surface markers such as immunoglobulin, la, H2, etc., will be examined by attempting to either mimic or inhibit the action of antigen, LPS, or T-cell factors with appropriate antisera. BIBLIOGRAPHIC REFERENCES: Kappler, J.W., Marrack (Hunter), P.C., Araneo, B.A., Jacobs, D. and Lord, E. T-cell subpopulations in the mouse. In: Interaction of radiation and host immune defense mechanisms in malignancy. (Conference, March, 1974, Greenbrier, W. Va.) BNL 50418 (Brookhaven National Laboratory Report, 1974) p. 245. Hoffman, M., Kappler, J.W., Hirst, J.A. and Oettgen, H.F. Regulation of the immune response. VI. ntibody-mediated inhibition of T and B-cell cooperation in the in vitro response to red blood cell antigens. Europ. J. Immunol. 4: 282, 1974.